Aromatic ring derivatives

Abstract

Novel aromatic ring derivatives represented by formula (I) or their pharmaceutical acceptable salts are provided. wherein Nu represents a 5- or 6-membered aromatic ring; ch 1 and ch 2 each represents a cross-linking group; and A represents an aromatic ring. These compounds have blood sugar-depressing activity or PDE 5 inhibitory activity and are useful as medicines for treating impaired glucose tolerance, diabetes, diabetic complications, syndrome of insulin-resistance, polycystic ovary syndrome, hyperlipidemia, atherosclerosis, cardiovascular disorders, hyperglycemia, hypertension, stenocardia, pulmonary hypertension, congestive heart failure, glomerulopathy, tubulointerstitial disorders, renal failure, angiostenosis, distal angiopathy, cerebral apoplexy, chronic reversible obstructions, autoimmune diseases, allergic rhinitis, urticaria, glaucoma, diseases characterized by enteromotility disorders, impotence, nephritis, cachexia, pancreatitis, restenosis after PTCA, etc.

What is claimed is:  
     
       1. A pharmaceutical composition which comprises, as an active ingredient, a heterocyclic aromatic ring compound of formula (I):                    
       wherein X indicates the substituent represented by formula (II);                    
       wherein R 2  represents a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a cyclo-lower alkyl group, an aromatic group, a heterocyclic aromatic group, or a heterocyclic group, each of which may have one or more substituents; ch 1  and ch 2  represent a saturated or unsaturated cross-linking group, which may be branched; ch 1  may have one or more substituents selected from a group consisting of a lower alkyl group, a lower cycloalkyl group, an aromatic group, a heterocyclic group, a lower alkyl-lower cycloalkyl group, an aromatic-lower alkyl group, and a heterocyclic lower alkyl group; Nu represents an imidazole ring; X and Nu may be bonded directly to each other; R 1  represents a hydrogen atom, a halogen atom, a lower alkyl group, an amino group, an acylamino group, a lower alkenyl group, a lower alkynyl group, a halo-lower alkyl group, a lower cycloalkyl group, a nitro group, a lower alkylamino group, a carboxyl group, an esterified carboxyl group, an amidated carboxyl group, a lower alkanesulfonyl group, an aromatic-sulfonyl group, a heterocyclic-aromatic-sulfonyl group, a hydroxyl group, or a lower alkoxyl group; n means a natural number of 2 or less; and A is an aromatic ring that may have one or more substituents; or its pharmaceutically acceptable salt.  
     
     
       2. The pharmaceutical composition of claim  1 , wherein the heterocyclic aromatic ring compound is represented by formula (I) where ch 1  is an ethylene chain or an ethenylene chain; ch 2  is a methylene chain; and R 1  is a hydrogen atom, a lower alkyl group, a halogen atom, or a phenyl group. 
     
     
       3. The pharmaceutical composition of claim  2 , wherein the heterocyclic aromatic ring compound is represented by formula (V) or formula (VI):                    
       wherein R 5  represents a hydrogen atom or a lower alkyl group; R 6  is a hydrogen atom, a halogen atom, or a phenyl group; and X and A are as defined above.  
     
     
       4. The pharmaceutical composition of claim  1 , wherein the aromatic ring compound is represented by formula (I) where X is a lower alkylsulfonylcarbamoyl group, a lower alkenylsulfonylcarbamoyl group, a lower alkynylsulfonylcarbamoyl group, an aromatic-sulfonylcarbamoyl group, a heterocyclic sulfonylcarbamoyl group, or a heterocyclic-aromatic-sulfonylcarbamoyl group, each of which may have one or more substituents. 
     
     
       5. A heterocyclic aromatic ring compound represented by formula (I):                    
       wherein X indicates the substituent represented by formula (II):                    
       wherein R 2  is a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a cyclo-lower alkyl group, an aromatic group, a heterocyclic aromatic group, or a heterocyclic group, each of which may have one or more substituents; ch 1  and ch 2  each represents a saturated or unsaturated cross-linking group, which may be branched; ch 1  may have one or more substituents selected from a group consisting of a lower alkyl group, a lower cycloalkyl group, an aromatic group, a heterocyclic aromatic group, a heterocyclic group, a lower alkyl-lower cycloalkyl group, an aromatic-lower alkyl group, a heterocyclic-aromatic-lower alkyl group, and a heterocyclic lower alkyl group; Nu represents an imidazole ring; X and Nu may be bonded directly to each other; R 1  represents a hydrogen atom, a halogen atom, a lower alkyl group, an amino group, an acylamino group, a lower alkenyl group, a lower alkynyl group, a halo-lower alkyl group, a lower cycloalkyl group, a nitro group, a lower alkylamino group, a carboxyl group, an esterified carboxyl group, an amidated carboxyl group, a lower alkanesulfonyl group, an aromatic-sulfonyl group, a heterocyclic-aromatic-sulfonyl group, a hydroxyl group, or a lower alkoxyl group; n means a natural number of 2 or less; and A is an aromatic ring that may have one or more substituents; and its pharmaceutically acceptable salt.  
     
     
       6. The heterocyclic aromatic ring compound and its pharmaceutically acceptable salt of claim  5 , wherein ch 1  is an ethylene chain or an ethenylene chain; ch 2  is a methylene chain; and R 1  is a hydrogen atom, a lower alkyl group, a halogen atom, or a phenyl group. 
     
     
       7. An heterocyclic aromatic ring compound represented by formula (V) or formula (VI):                    
       wherein R 5 , R 6 , X and A are as defined above; and its pharmaceutically acceptable salt.  
     
     
       8. The heterocyclic aromatic ring compound and its pharmaceutically acceptable salt of claim  5 ,  6  or  7 , wherein X is a lower alkylsulfonylcarbamoyl group, a lower alkenyl-sulfonylcarbamoyl group, a lower alkynylsulfonylcarbamoyl group, an aromatic-sulfonylcarbamoyl group, a heterocyclic-aromatic-sulfonylcarbamoyl group, or a heterocyclic sulfonylcarbamoyl group each of which may have one or more substituents. 
     
     
       9. A method for preventing or treating impaired glucose tolerance, diabetes, diabetic complications, syndrome of insulin resistance, polycystic ovary syndrome, hyperlipidemia, atherosclerosis, cardiovascular disorders, hyperglycemia, and hypertension comprising administering to a patient in need thereof an effective amount of a heterocyclic aromatic ring compound represented by formula (I):                    
       wherein x indicates the substituent represented by formula (II):                    
       wherein R 2  represents a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a cyclo-lower alkyl group, an aromatic group, a heterocyclic aromatic group, or a heterocyclic group, each of which may have one or more substituents; ch 1  and ch 2  represent a saturated or unsaturated cross-linking group, which may be branched; ch 1  may have one or more substituents selected from a group consisting of a lower alkyl group, a lower cycloalkyl group, an aromatic group, a heterocyclic aromatic group, a heterocyclic group, a lower alkyl-lower cycloalkyl group, an aromatic-lower alkyl group, a heterocyclic-aromatic-lower alkyl group, and a heterocyclic lower alkyl group; Nu represents an imidazole ring; X and Nu may be bonded directly to each other; R 1  represents a hydrogen atom, a halogen atom, a lower alkyl group, an amino group, an acylamino group, a lower alkenyl group, a lower alkynyl group, a halo-lower alkyl group, a lower cycloalkyl group, a nitro group, a lower alkylamino group, a carboxyl group, an esterified carboxyl group, an amidated carboxyl group, a lower alkanesulfonyl group, an aromatic-sulfonyl group, a heterocyclic-aromatic-sulfonyl group, a hydroxyl group, or a lower alkoxyl group; n means a natural number of 2 or less; and A is an aromatic ring that may have one or more substituents; or its pharmaceutically acceptable salt.  
     
     
       10. A method for lowering blood sugar levels, which comprises administering an effective amount of the compound of claim  5  to a patient in need thereof.